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Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla.

McCaughtry TM, Baldwin TA, Wilken MS, Hogquist KA - J. Exp. Med. (2008)

Bottom Line: However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation.We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation.Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c(+) cortical dendritic cells, and elimination of such cells impaired deletion.

View Article: PubMed Central - PubMed

Affiliation: Center for Immunology, Laboratory Medicine, and Pathology, University of Minnesota, Minneapolis, MN 55454, USA.

ABSTRACT
The thymic medulla is generally held to be a specialized environment for negative selection. However, many self-reactive thymocytes first encounter ubiquitous self-antigens in the cortex. Cortical epithelial cells are vital for positive selection, but whether such cells can also promote negative selection is controversial. We used the HY(cd4) model, where T cell receptor for antigen (TCR) expression is appropriately timed and a ubiquitous self-antigen drives clonal deletion in male mice. We demonstrated unambiguously that this deletion event occurs in the thymic cortex. However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation. We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation. Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c(+) cortical dendritic cells, and elimination of such cells impaired deletion.

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CCR7 is dispensable for clonal deletion of HYcd4 thymocytes. (A) The expression of CCR7 on female and male T3.70+ thymocytes from HYcd4 mice on a WT or Bimo background. (B) BM from female HYcd4 mice on either WT or CCR7° background was mixed with WT female or male BM and transferred into WT female or male recipients. Activation of Caspase 3 in T3.70+ thymocytes of the indicated genotype is depicted. Data represent the mean from four individuals from one experiment ± SD. P = 0.0002 when comparing either WT males and females or CCR7° males and females. The difference between WT males and CCR7° males was not significant. (C) HYcd4 Dbo BM was mixed with WT or plt/plt female or male BM and transferred into WT or plt/plt female or male mice. The expression of CD69 and PD-1 on T3.70+ thymocytes from the indicated group is shown. (D) The activation of Caspase 3 on T3.70+ thymocytes. Data depicts the mean ± SD. The fold change is indicated. P = 0.0066. Data are representative of three separate experiments.
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fig4: CCR7 is dispensable for clonal deletion of HYcd4 thymocytes. (A) The expression of CCR7 on female and male T3.70+ thymocytes from HYcd4 mice on a WT or Bimo background. (B) BM from female HYcd4 mice on either WT or CCR7° background was mixed with WT female or male BM and transferred into WT female or male recipients. Activation of Caspase 3 in T3.70+ thymocytes of the indicated genotype is depicted. Data represent the mean from four individuals from one experiment ± SD. P = 0.0002 when comparing either WT males and females or CCR7° males and females. The difference between WT males and CCR7° males was not significant. (C) HYcd4 Dbo BM was mixed with WT or plt/plt female or male BM and transferred into WT or plt/plt female or male mice. The expression of CD69 and PD-1 on T3.70+ thymocytes from the indicated group is shown. (D) The activation of Caspase 3 on T3.70+ thymocytes. Data depicts the mean ± SD. The fold change is indicated. P = 0.0066. Data are representative of three separate experiments.

Mentions: A summary of mixed BM chimeras generated for these studies


Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla.

McCaughtry TM, Baldwin TA, Wilken MS, Hogquist KA - J. Exp. Med. (2008)

CCR7 is dispensable for clonal deletion of HYcd4 thymocytes. (A) The expression of CCR7 on female and male T3.70+ thymocytes from HYcd4 mice on a WT or Bimo background. (B) BM from female HYcd4 mice on either WT or CCR7° background was mixed with WT female or male BM and transferred into WT female or male recipients. Activation of Caspase 3 in T3.70+ thymocytes of the indicated genotype is depicted. Data represent the mean from four individuals from one experiment ± SD. P = 0.0002 when comparing either WT males and females or CCR7° males and females. The difference between WT males and CCR7° males was not significant. (C) HYcd4 Dbo BM was mixed with WT or plt/plt female or male BM and transferred into WT or plt/plt female or male mice. The expression of CD69 and PD-1 on T3.70+ thymocytes from the indicated group is shown. (D) The activation of Caspase 3 on T3.70+ thymocytes. Data depicts the mean ± SD. The fold change is indicated. P = 0.0066. Data are representative of three separate experiments.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2571932&req=5

fig4: CCR7 is dispensable for clonal deletion of HYcd4 thymocytes. (A) The expression of CCR7 on female and male T3.70+ thymocytes from HYcd4 mice on a WT or Bimo background. (B) BM from female HYcd4 mice on either WT or CCR7° background was mixed with WT female or male BM and transferred into WT female or male recipients. Activation of Caspase 3 in T3.70+ thymocytes of the indicated genotype is depicted. Data represent the mean from four individuals from one experiment ± SD. P = 0.0002 when comparing either WT males and females or CCR7° males and females. The difference between WT males and CCR7° males was not significant. (C) HYcd4 Dbo BM was mixed with WT or plt/plt female or male BM and transferred into WT or plt/plt female or male mice. The expression of CD69 and PD-1 on T3.70+ thymocytes from the indicated group is shown. (D) The activation of Caspase 3 on T3.70+ thymocytes. Data depicts the mean ± SD. The fold change is indicated. P = 0.0066. Data are representative of three separate experiments.
Mentions: A summary of mixed BM chimeras generated for these studies

Bottom Line: However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation.We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation.Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c(+) cortical dendritic cells, and elimination of such cells impaired deletion.

View Article: PubMed Central - PubMed

Affiliation: Center for Immunology, Laboratory Medicine, and Pathology, University of Minnesota, Minneapolis, MN 55454, USA.

ABSTRACT
The thymic medulla is generally held to be a specialized environment for negative selection. However, many self-reactive thymocytes first encounter ubiquitous self-antigens in the cortex. Cortical epithelial cells are vital for positive selection, but whether such cells can also promote negative selection is controversial. We used the HY(cd4) model, where T cell receptor for antigen (TCR) expression is appropriately timed and a ubiquitous self-antigen drives clonal deletion in male mice. We demonstrated unambiguously that this deletion event occurs in the thymic cortex. However, the kinetics in vivo indicated that apoptosis was activated asynchronously relative to TCR activation. We found that radioresistant antigen-presenting cells and, specifically, cortical epithelial cells do not efficiently induce apoptosis, although they do cause TCR activation. Rather, thymocytes undergoing clonal deletion were preferentially associated with rare CD11c(+) cortical dendritic cells, and elimination of such cells impaired deletion.

Show MeSH
Related in: MedlinePlus